Graduate student Yonsei University College of Medicine, Republic of Korea
Abstract: The endometrium plays a vital role in blastocyst implantation during the implantation window, a period of peak receptivity regulated by estrogen, progesterone, and growth factors. However, existing in vitro models fail to accurately replicate the native tissue environment and its functions. This study presents a novel in vitro implantation model incorporating endometrial organoids (EOs) and stromal cell cultures within a decellularized uterus extracellular matrix (UEM) to better simulate physiological conditions. Mouse-derived EOs were successfully cultured and encapsulated in UEM, exhibiting formation efficiencies comparable to Matrigel. Hormonal treatment with estradiol and progesterone enhanced mucin secretion and proliferation, demonstrating the EOs’ functional mimicry of endometrial tissue. In vivo, the combination of EOs and UEM effectively restored thin endometrium, significantly increasing epithelial thickness and reducing fibrosis. All treated mice achieved successful pregnancies. Co-culturing stromal cells with EOs in UEM facilitated epithelial monolayer formation, while GFP-labeled E3.5 blastocysts migrated toward the basal layer. Additionally, EOs cultured in UEM exhibited higher expression of endometrial genes and greater hormone responsiveness compared to Matrigel. These findings underscore UEM's potential in promoting endometrial regeneration and function, leading to improved pregnancy outcomes and reduced fibrosis.
Funding Source: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2021R1C1C2009131) and the Brain Korea 21 Project for Medical Science, Yonsei University.
